SACHA: Accelerate children’s access to innovative molecules – Interview with Dr. Pablo Berlanga

France is a pioneer in Europe in the development of new drugs in pediatric oncology. For example, within the ITCC network (Innovative Therapies for Children and adolescents with Cancer, 14 countries), France accounts for 50% of inclusions in early clinical trials.

Since 2014, specific measures have been put in place in France as part of the Cancer Plan to increase and facilitate access to innovations for children and adolescents experiencing therapeutic failure:

  • AcSé-ESMART program: early phase, multi-arm, multi-drug trial for young patients having a deep molecular analysis of their tumor.
  • Creation of 7 Labeled Early Phase Centers (CLIP2) adults – children.

Despite this strong dynamic of expanding the panel of trials of new drugs in France, the therapeutic offer remains insufficient and pediatric oncologists and hematologists prescribe innovative drugs either within the framework of compassionate/early access (formerly called ATU, Authorization Temporary Use) or off-label (Marketing Authorization), for drugs already approved for adults. However, before SACHA, we had no idea about the number of these prescriptions, nor about the toxicity and effectiveness of these treatments.

SACHA aims at securing access to these innovative therapies outside the framework of clinical trials. This project is a French observational study, which is now being deployed internationally, and which consists of a prospective collection of toxicity and effectiveness data for these innovative therapies, prescribed as part of compassionate/early access.

Results of the SACHA France trial:

To find out more about this visionary program, we went to meet Dr. Pablo Berlanga, pediatric oncologist at the Gustave Roussy Institute, and responsible for this wonderful project, financed for more than 4 years by Imagine for Margo.

1- Can you introduce yourself and explain to us what brought you to pediatric oncology?

I always wanted to be a pediatrician with a specialization in pediatric oncology. This discipline has interested me greatly since my medical studies. At that time, I was a volunteer in an association based in Spain which took care of children suffering from cancer and who were hospitalized. Moreover, later, as a doctor, I happened to follow some of these children. I always enjoyed being in contact with them. In addition, their cancer has specificities and complexities that are very different from adult forms and it fascinates me to understand the reasons and to be able, of course, to better treat this disease.

2- What were the issues and needs that motivated you to do SACHA?

We are very lucky that France has one of the largest portfolios of clinical trials in Europe. However, prior to 2019, before SACHA began, we did not collect data from patients treated with investigational drugs outside of clinical trials. We also realized that we could not even estimate how many patients in France were receiving these new drugs. This is why the SFCE New Medicines Committee had the idea of creating SACHA. We wanted to secure access to these innovative treatments, prescribed as part of compassionate/early access or off-label, when the treatment had been authorized in adults.

To achieve this goal, we first had to figure out how to collect toxicity and efficacy data from each patient. Then, we had to analyze them to see if we could draw conclusions and write medical recommendations, by type of cancer, for all pediatric oncologists.

3- What were the keys to SACHA’s success in France? 

SACHA is a collaborative SFCE project that responds to a patient need. This project was clearly identified as a priority by all members of the SFCE and was developed by the “new drugs” committee. This made it possible to form a solid basis for starting the project and to communicate well and convince people of its importance. We organized a steering committee with coordinating doctors from OIR (Interregional Hospital Organizations), who were able to involve the different centers and the Gustave Roussy pharmacovigilance team, which plays a fundamental role in SACHA, in this project. In the steering committee, there are also 2 clinical research associates who ensure quality filling of the information collected in a centralized and secure database. Since 2023, we have also had representatives of associations/patients on this steering committee, Imagine for Margo in this case. Thanks to this multidisciplinary team, we were able to show that the project works, which further motivated the members of the SFCE to continue to follow us in this adventure.

4- How is a patient recruited in SACHA?

In France, when a patient is in relapse, we are fortunate to be able to offer them complete molecular profiling of their tumor. This is made possible thanks to various studies notably financed by Imagine for Margo such as MappyActs. The success of these projects has also made it possible to continue these profilings in the France Génomique 2025 national program. In light of the results obtained, we, the doctors, discuss in a national multidisciplinary meeting the best therapeutic options to give to the patient. Sometimes, the patient cannot be included in a clinical trial and we fall back on an innovative treatment for which there is strong suspicion of effectiveness. The final decision is of course always made by the doctor, after discussion with the patient and his/her family. If treatment is started, that’s when we talk to patients and families about SACHA and if they agree, the doctor can include their patient in SACHA.

5- Thanks to SACHA, we secure prescriptions for innovative medicines. But can SACHA also collect data after the clinical trial and before the drug is placed on the market?

Yes indeed. This is precisely the case for the BEACON Immuno trial on neuroblastoma, also co-funded by Imagine for Margo. In this trial, we combined conventional chemotherapy with immunotherapy (chemo-immunotherapy). Patient inclusion ended in February 2021 and we became aware of the first results in June 2022, which were presented at the ASCO (American Society of Clinical Oncology) international congress. It turns out that this combination doubles the chances of having a favorable response in patients with high-risk or relapsed neuroblastoma. This immunotherapy has marketing authorization in France but not for this indication. As a result, the SFCE Neuroblastoma committee has developed recommendations for treatment with chemo-immunotherapy and we are therefore prescribing this treatment off-label. We collected the data in SACHA which refined our knowledge on the toxicity and effectiveness of this treatment. These data, which we have just published, are complementary to the BEACON Immuno study and could also help the manufacturer, who produces the immunotherapy agent, to request an extension of the indication of its Marketing Authorization.

6- Is SACHA also applicable in another case?

Yes, indeed. This is particularly the case for Larotrectonib. This innovative drug was validated in 2020 by the HAS (French High Authority of Health), for its use in pediatric cancers located outside the brain. In fact, this authority gave a conditional reimbursement agreement: we can give the drug but it is necessary to collect real-life data to confirm the study initially carried out by Dr. Daniel Orbach (Tag-N-TRAK, also co-funded by Imagine for Margo). As a result, in order to satisfy this request from the HAS, this treatment was included in SACHA and we have been following 19 patients for 4 years. HAS recognized SACHA in 2023 as a source of data that can be used for early access but also for an evaluation of treatments after they can be marketed. 

7- Do you alert doctors when you realize that an experimental drug is too toxic or too ineffective?

Yes indeed, one of the objectives of SACHA is to write therapeutic recommendations. The real-life data of each patient is analyzed by the pharmacovigilance team of the Gustave Roussy Institute. They will list and evaluate all unexpected and/or significant toxicities from these treatments. These data are reported and discussed with the SACHA steering committee, which meets every two months to evaluate these data. For example, we had the case of a patient treated for 15 months with Tazemetostat and who reported a second cancer. This was the second time this has happened in a child with this treatment worldwide. We therefore passed on the information to all SFCE centers and to the competent authorities, which allows us to increase the vigilance of doctors when they prescribe it despite everything, in the absence of any other therapeutic possibility.

In addition, the other strong point of the study is to provide information related to the effectiveness of medications. We inform our colleagues if no effect is observed or if, conversely, the patients have responded well and their disease is progressing positively.

8- Can you explain to us what real-life data are?

That’s a very good question. Real-life patient data consist of all clinical data that can be measured or evaluated and that are collected while the patient is receiving treatment. These data can be collected retrospectively. But this has biases. In SACHA, we have chosen to collect them prospectively, in order to ensure adequate data collection.

9- SACHA made it possible to collect data on 650 patients at the end of 2023. Were you able to identify effective drugs not yet evaluated in a clinical trial?

This is a very good question, because it is very important to say that SACHA is not a clinical trial, but meets real needs. For example, we observed that the most prescribed drugs are inhibitors of the MEK and BRAF pathways, which showed effectiveness in clinical trials conducted between 2017 and 2020. Now that these protocols are closed, patients benefit from these drugs through compassionate/early or off-label access. We collect data in SACHA to strengthen those obtained in clinical trials. In addition, we also noticed in SACHA that a patient treated with another inhibitor (ME) had responded positively, but transiently. So, thanks to these data, we were able to develop a new arm in the AcSé-eSMART trial, where this drug is tested in combination with another molecule.

10- HAS (French High Authority of Health) has recognized SACHA as a source of data that can be used and is also supported by the ANSM (French National Agency for the Safety of Medicines and Health Products). What positive consequences does this have for patients?

The objective of the HAS is to ensure the benefits of a medicine for society and therefore wishes to collect efficacy and toxicity data in real time, in particular for innovative medicines. We are collaborating with HAS for this purpose. For example, we confirmed the very high efficacy and low toxicity of Larotrectinib. The HAS was thus able to confirm in 2023 its initial opinion given in 2020 and extend the conditional marketing authorization given for this innovative medicine.

We are also supported by the ANSM, and have been since the start, in 2019. The ANSM has been fundamental support for SACHA, especially since this agency is responsible for compassionate access to medicines. Since 2021, we have had an even closer collaboration with the ANSM. We share a lot more information and we give them an annual report including the drugs they have authorized. The ANSM therefore actively recommends the inclusion of patients in SACHA. We therefore have a give-and-take relationship with this organization and the results of our collaboration were presented at ASCO 2023.

11- Now that SACHA has been published and is recognized by the ANSM and the HAS, will this method be applied to other pathologies, such as rare diseases?

As for SACHA, the method can obviously be extrapolated to other therapeutic areas, but in my opinion we should start in the same way, namely by forming a group of experts who have the capacity to bring together all the stakeholders. . We are lucky to have an incredible structure in France for pediatric cancers: our dear SFCE and its 31 pediatric centers. This structure is a real opportunity for patients and was essential for building SACHA. The ability we have to work together is something unique on a global level and certainly explains why France is a leader in access to therapeutic innovation in childhood cancers.

12- Now you are developing SACHA internationally. Are you going to proceed in the same way, via local centers which will report patients’ real-life data?

In order to expand SACHA internationally, we work with the different countries that make up the ITCC (Innovative Therapies for Children and adolescents with Cancer) network. Each country adapts the SACHA method to its regulations. Together, we collect the same types of data in the same databases, with the same methodology.

13- Imagine for Margo is very involved in the SACHA project. In addition to the funding provided, we have participated in the project steering committee since its beginnings. What do associations like Imagine for Margo bring to pediatric oncology?

Our collaboration is fundamental because, thanks to you, we were able to build SACHA. Without your funding and support, we would never have been able to do something this innovative. On the other hand, I find that the other real added value of Imagine for Margo is also your ability to make us think and enrich our thoughts. With the SACHA management team, I discuss medical and scientific aspects or pharmacovigilance data. With you, our discussions and your reflections are changing our vision of medicine and allowing us to be even more focused on the reality and needs of patients. Finally, SACHA was published in order to be shared within the academic community, but this project must also directly benefit patients. Thanks to you and your support, our data and our projects are seen as more convincing and more impactful by health authorities.